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Protein

Growth/differentiation factor 5

Gene

Gdf5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (By similarity). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (By similarity). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (PubMed:24076600). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • BMP signaling pathway Source: GO_Central
  • cell development Source: GO_Central
  • chondroblast differentiation Source: MGI
  • chondrocyte differentiation Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • forelimb morphogenesis Source: MGI
  • growth Source: InterPro
  • hindlimb morphogenesis Source: MGI
  • mitophagy in response to mitochondrial depolarization Source: Ensembl
  • negative regulation of chondrocyte differentiation Source: MGI
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of mesenchymal cell apoptotic process Source: MGI
  • negative regulation of neuron apoptotic process Source: Ensembl
  • positive regulation of BMP signaling pathway Source: MGI
  • positive regulation of chondrocyte differentiation Source: MGI
  • positive regulation of neuron differentiation Source: Ensembl
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: GO_Central
  • regulation of MAPK cascade Source: GO_Central
  • regulation of multicellular organism growth Source: MGI
  • SMAD protein import into nucleus Source: MGI
  • SMAD protein signal transduction Source: MGI
  • transmembrane receptor protein serine/threonine kinase signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Chondrogenesis

Enzyme and pathway databases

ReactomeiR-MMU-2129379. Molecules associated with elastic fibres.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 5
Short name:
GDF-5
Alternative name(s):
Bone morphogenetic protein 14
Short name:
BMP-14
Gene namesi
Name:Gdf5
Synonyms:Bmp14, Bp, Gdf-5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:95688. Gdf5.

Subcellular locationi

  • Secreted By similarity
  • Cell membrane By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Defects in Gdf5 are the cause of brachypodism (bp) which alters the length and numbers of bones in the limbs but spares the axial skeleton.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
PropeptideiPRO_000003391428 – 375Sequence analysisAdd BLAST348
ChainiPRO_0000033915376 – 495Growth/differentiation factor 5Add BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi183N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi394 ↔ 460By similarity
Disulfide bondi423 ↔ 492By similarity
Disulfide bondi427 ↔ 494By similarity
Disulfide bondi459InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43027.
PRIDEiP43027.

PTM databases

iPTMnetiP43027.
PhosphoSitePlusiP43027.

Expressioni

Inductioni

Induced over 300-fold in tibialis anterior muscles 3 days following denervation. High expression is maintained at least until 10 days after denervation.1 Publication

Gene expression databases

BgeeiENSMUSG00000038259.
CleanExiMM_GDF5.
GenevisibleiP43027. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Interacts with serine proteases, HTRA1 and HTRA3 (PubMed:15206957, PubMed:14973287). Following LPS binding, may form a complex with CXCR4, HSP90AA1 and HSPA8 (By similarity). Interacts with high affinity with NOG; inhibits chondrogenesis (By similarity). Interacts with high affinity with BMPR1B and lower affinity with BMPR1A; positively regulates chondrocyte differentiation and induces SMAD-dependent signaling. Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199888. 2 interactors.
STRINGi10090.ENSMUSP00000048079.

Structurei

3D structure databases

ProteinModelPortaliP43027.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43027.
KOiK04664.
OMAiEPKEPFR.
OrthoDBiEOG091G09KP.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 2 hits.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43027-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLPKLLTLL LWHLAWLDLE LICTVLGAPD LGQRTPGAKP GLTKAEAKER
60 70 80 90 100
PPLARNVFRP GGHIYGVGAT NARAKGSSGQ TQAKKDEPRK MPPRSGGPET
110 120 130 140 150
KPGPSSQTRQ AAARTVTPKG QLPGGKASSK AGSAPSSFLL KKTREPGTPR
160 170 180 190 200
EPKEPFRPPP ITPHEYMLSL YRTLSDADRK GGNSSVKLEA GLANTITSFI
210 220 230 240 250
DKGQDDRGPA VRKQRYVFDI SALEKDGLLG AELRILRKKP LDVAKPAVPS
260 270 280 290 300
SGRVAQLKLS SCPSGRQPAA LLDVRSVPGL DGSGWEVFDI WKLFRNFKNS
310 320 330 340 350
AQLCLELEAW ERGRAVDLRG LGFERTARQV HEKALFLVFG RTKKRDLFFN
360 370 380 390 400
EIKARSGQDD KTVYEYLFSQ RRKRRAPLAN RQGKRPSKNL KARCSRKALH
410 420 430 440 450
VNFKDMGWDD WIIAPLEYEA FHCEGLCEFP LRSHLEPTNH AVIQTLMNSM
460 470 480 490
DPESTPPTCC VPTRLSPISI LFIDSANNVV YKQYEDMVVE SCGCR
Length:495
Mass (Da):54,895
Last modified:July 27, 2011 - v2
Checksum:i8FAECD5A9C996D6E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti98P → S.2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08337 mRNA. Translation: AAA18778.1.
AL845445 Genomic DNA. Translation: CAM22612.1.
CH466551 Genomic DNA. Translation: EDL06156.1.
BC034546 mRNA. Translation: AAH34546.1.
CCDSiCCDS16958.1.
PIRiS43294.
RefSeqiNP_032135.2. NM_008109.3.
UniGeneiMm.4744.

Genome annotation databases

EnsembliENSMUST00000040162; ENSMUSP00000048079; ENSMUSG00000038259.
GeneIDi14563.
KEGGimmu:14563.
UCSCiuc012chg.1. mouse.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08337 mRNA. Translation: AAA18778.1.
AL845445 Genomic DNA. Translation: CAM22612.1.
CH466551 Genomic DNA. Translation: EDL06156.1.
BC034546 mRNA. Translation: AAH34546.1.
CCDSiCCDS16958.1.
PIRiS43294.
RefSeqiNP_032135.2. NM_008109.3.
UniGeneiMm.4744.

3D structure databases

ProteinModelPortaliP43027.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199888. 2 interactors.
STRINGi10090.ENSMUSP00000048079.

PTM databases

iPTMnetiP43027.
PhosphoSitePlusiP43027.

Proteomic databases

PaxDbiP43027.
PRIDEiP43027.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040162; ENSMUSP00000048079; ENSMUSG00000038259.
GeneIDi14563.
KEGGimmu:14563.
UCSCiuc012chg.1. mouse.

Organism-specific databases

CTDi8200.
MGIiMGI:95688. Gdf5.

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43027.
KOiK04664.
OMAiEPKEPFR.
OrthoDBiEOG091G09KP.
TreeFamiTF316134.

Enzyme and pathway databases

ReactomeiR-MMU-2129379. Molecules associated with elastic fibres.

Miscellaneous databases

PROiP43027.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038259.
CleanExiMM_GDF5.
GenevisibleiP43027. MM.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 2 hits.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGDF5_MOUSE
AccessioniPrimary (citable) accession number: P43027
Secondary accession number(s): A2ARK2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.